Influenza A viruses cause a highly contagious, acute respiratory disease responsible for human suffering and economic burden every winter. Vaccination is a primary means for prophylaxis against influenza infection, and inactivated and live attenuated influenza virus vaccines are currently available. Inactivated vaccines, administered parenterally, are generally 70% to 90% effective for reducing the incidence of clinical illness in healthy persons as long as the antigenicities of the circulating virus strains match those of the vaccine (Cox et al., 1999). However, because mucosal immunity and cytotoxic T-cell responses are limited, protective efficacy of inactivated vaccines lasts for only a short period, requiring annual vaccination. In contrast, live attenuated influenza virus vaccines are intranasally administered and elicit robust mucosal immunity and cellular responses; their protective efficacy, therefore, lasts for longer periods (Cox et al., 2004). Only two live attenuated vaccines are currently on the market, and use of these vaccines in the United States is limited to persons aged 2 to 49 years (CDC, 2007).
Generally, influenza vaccines have been prepared from live, attenuated virus or killed virus which can grow to high titers. Live virus vaccines activate all phases of the immune system and stimulate an immune response to each of the protective antigens, which obviates difficulties in the selective destruction of protective antigens that may occur during preparation of inactivated vaccines. In addition, the immunity produced by live virus vaccines is generally more durable, more effective, and more cross-reactive than that induced by inactivated vaccines. Further, live virus vaccines are less costly to produce than inactivated virus vaccines. However, the mutations in attenuated virus are often ill-defined.
For the existing seasonal human influenza, both inactivated virus vaccine and live attenuated virus vaccine are available. In April 2007, the U.S. Food and Drug Administration (FDA) announced the first approval of an inactivated vaccine for humans against the H5N1 virus. However, the available data indicate that inactivated H5 influenza vaccines are suboptimal in their immunogenicity, and a large amount of hemagglutinin (HA) glycoprotein or coadministration of an adjuvant is required to achieve an adequate immune response (Bressen et al., 2006; Lin et al., 2006; Nicholson et al.; 2005; Stephenson et al., 2003; Treanor et al.; 2006).